The goal of this project is to improve the treatment of superficial bladder cancer through the use of directed gold nanorods. Bladder cancer is a common cancer with 68,810 new cases annually in the United States. Most of these cases are initially superficial and treated with cystoscopic resection and drug therapy administered directly into the bladder via a catheter. Despite these treatments, approximately 40% of those with superficial bladder cancer experience recurrent disease requiring additional treatment and are at risk of developing a progressive and lethal form of disease. This application uses an innovative application of nanotechnology, capitalizing on the presence of a differentially expressed therapeutic target commonly observed in bladder cancer - the epidermal growth factor receptor (EGFR). While several pre-clinical investigations have evaluated the effectiveness of nanoparticles in cancer treatment, the difficulty of drug delivery has emerged as an obstacle in systemic delivery. Using gold nanorods linked to antibodies against the tumor-associated marker EGFR (nano-1EGFR), gold nanorods will specifically associate with bladder cancer cells in vitro. We hypothesize that the strong Plasmon resonance of the targeted gold-nanorod will lead to significant local heating, to the point of thermal ablation, with the application of laser treatment. In our proposed research plan, the first aim will investigate and optimize the nano-1EGFR concentration and laser power/duration for cellular killing. The second aim will take the in vitro findings of Aim 1 and translate these in the in vivo setting. An orthotopic bladder cancer mouse model will be used to assess the minimal nano- 1EGFR concentration and shortest dwell time needed for adequate in vivo binding. The final aim will investigate the safety and efficacy of this approach in vivo, using the mouse model. Progressive "dose escalation" of external laser treatments will be performed before a final multi-arm trial of this approach to firmly establish its efficacy compared to appropriate control arms. PUBLIC HEALTH RELEVANCE: Bladder cancer is a common cancer with 68,810 new cases annually in the United States, noting that most of these cases are initially superficial and treated with cystoscopic resection and with drug therapy administered directly into the bladder via a catheter. Despite these treatments, approximately 40% of those with superficial bladder cancer experience recurrent disease requiring additional treatment and are at risk of developing a progressive and lethal form of disease. Improved therapy for superficial bladder cancer therefore represents a significant clinical need and is the focus of this application.